Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acid-base homeostasis depends on glutamine flow from producer organs to those capable of generating bicarbonate. Glutamine oxidation, the prerequisite metabolic transformation, can be expressed by many sites; however, net base generation requires that glutamine flow be directed to a specific organ, the kidney. Normally, glutamine flows from the periphery to the splanchnic bed, providing a major fuel and supporting ureagenesis. Glutamine flow in chronic metabolic acidosis, on the other hand, is rerouted to the kidneys; asymmetrical distribution of NH+4 and HCO3- into the urine and renal vein subserves restoration of alkaline reserves. Clearly, glutamine flows in accordance with physiological demands, yet little is known of the regulatory mechanisms. As a model, chronic metabolic acidosis alters two aspects of this vital flow, its direction and magnitude. Characteristically the direction of flow is away from the splanchnic bed and into the kidneys associated with a marked fall in arterial glutamine concentration, restoring arterial level returns flow to the splanchnic bed sink. Thus glutamine homeostasis is sacrificed to impart direction to interorgan glutamine flow. Although multiple sites contribute to glutamine homeostasis, of great strategic importance is the potent hepatic glutaminase flux activated by portal venous NH+4 fed forward by gut metabolism; local hydrogen ion concentration modulates the effectiveness of this activator. Acute regulation of flow direction can be exerted by the lungs in determining the prevailing pCO2 and cellular acidity; respiratory compensation in chronic acidosis allows the expression of hepatic glutaminase, thereby suppressing arterial glutamine concentration. The enormous magnitude of glutamine flowing from muscle to the kidneys is supported by adaptive increases in glutamine synthetase and mitochondrial glutaminase, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interorgan glutamine flow in metabolic acidosis. 332 41

D-Glutamate (Glu) was previously shown to block L-Glu uptake and accelerate glutaminase flux in cultured kidney cells [Welbourne, T. C., and D. Chevalier. Am. J. Physiol. 272 (Endocrinol. Metab. 35): E367-E370, 1997]. To test whether D-Glu would be taken up by the intact functioning kidney and effect the same response in vivo, male Sprague-Dawley rats were infused with D-Glu (2.6 mumol/min), and renal uptake of D- and L-Glu was determined from chemical and radiolabeled arteriovenous Glu concentration differences times renal plasma flow. The amount removed was then compared with that amount filtered to obtain the antiluminal contribution. In the controls, L-Glu uptake measured as net removal was 33% of the arterial L-Glu load and not different from that filtered, 27%; however, the unidirectional uptake was actually 58% of the arterial load, indicating that antiluminal uptake contributes at least half to the overall Glu consumption. Surprisingly, the kidneys showed a more avid removal of D-Glu, removing 73% of the arterial load, indicating uptake predominantly across the antiluminal cell surface. Furthermore, uptake of D-Glu was associated with a 55% reduction in L-Glu uptake, with the residual amount taken up equivalent to that filtered; D-Glu did not increase the excretion of the L-isomer. However, elevating plasma L-Glu concentration reduced uptake of the D-isomer, suggesting a shared antiluminal transporter. Thus there is an apparent asymmetrical distribution of the D-Glu transporter. Under these conditions, kidney cortex L-Glu content decreased 44%, whereas net glutamine (Gln) uptake increased sevenfold (170 +/- 89 to 1,311 +/- 219 nmol/min, P < 0.01) and unidirectional uptake nearly threefold (393 +/- 121 to 1,168 +/- 161 nmol/min, P < 0.05); this large Gln consumption was paralleled by an increase in ammonium production so that the ratio of production to consumption approaches 2, consistent with accelerated Gln deamidation and subsequent Glu deamination. These results point to a functional asymmetry (antiluminal vs. luminal) for Glu transporter activity, which potentially plays an important role in modulating Gln metabolism and renal function.
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PMID:Glutamate transport asymmetry in renal glutamine metabolism. 961 46